What health implications may be associated with a change in both copies of the CEP120 gene?
Patients carrying mutations in both copies of the CEP120 gene can present a wide spectrum of severity, from relatively mild, purely neurological phenotypes to severe, lethal conditions characterized by malformations of several organs. The phenotype is not predictable based on the type of mutation, though the founder mutation c.595G>C (p.Ala199Pro) seems to be consistently associated to skeletal defects. There is usually a good degree of phenotypic consistency within families, albeit intra-familial variability cannot be excluded “a priori”, as this has been reported in some ciliopathy families (related to mutations in distinct ciliopathy genes).
Features associated to CEP120 mutations can include:
- Hypotonia in neonatal age
- Malformation of the cerebellum and brainstem (“molar tooth sign”)
- Occipital encephalocele
- Developmental delay/intellectual disability
- Abnormal ocular movements
- Ataxia
- Behavioral problems
- Narrow thorax with short ribs
- Short limbs
- Dysplastic pelvis
- Polydactyly, other digit anomalies
- Orofacial defects (cleft lip/palate, tongue hamartomas, bifid tongue, multiple frenula)
- Cystic kidneys
- Other malformations (ambiguous genitalia, anal atresia)